1. Field of the Invention
The present invention relates to a method of detecting a biomolecule using a field effect transistor (FET), and more particularly, to a method of electrically sensing a bond between a probe biomolecule and a target biomolecule.
2. Description of the Related Art
Biosensors, which include transistors, are sensors that electrically sense biomolecules. Biosensors are manufactured using semiconductor processes, quickly convert electric signals, and can be easily applied to integrated circuits (ICs) and MEMS. Due to these advantages, much research has gone into biosensors.
U.S. Pat. No. 4,238,757 was the first Patent regarding the detection of biological reactions using a FET, and is directed to a biosensor capable of identifying an antigen-antibody reaction by detecting a current that varies due to a change in the surface charge concentration of a semiconductor inversion layer. This patent is directed toward a biosensor for sensing proteins. In U.S. Pat. No. 4,777,019 biological monomers are adsorbed onto the surface of a gate, and hybridization between the biological monomers and complementary monomers is measured using a FET. U.S. Pat. No. 5,846,708 discloses a method of sensing hybridization using a charged coupled device (CCD). In this method, the hybridization can be identified using a phenomenon that bonded biomolecules absorb light. In U.S. Pat. Nos. 5,466,348 and 6,203,981, a TFT is used and a S/N ratio is improved by application to a circuit.
A thin film transistor (TFT) has lower manufacturing costs than a transistor formed on a silicon substrate, and a TFT enables the formation of an array-type chip with increased integrity by increasing the area of a substrate. An FET used as a biosensor has lower costs and requires less time than other conventional methods. In addition, an FET can be easily applied to integrated circuit (IC)/MEMS processes.
FIG. 1 is a sectional view of a typical bioFET. Referring to FIG. 1, a source 12a and a drain 12b are respectively formed in side portions of a substrate 11 doped with an n- or p-type material. The source 12a and the drain 12b are of an opposite conductivity type to the substrate 11. A gate 13 contacting the source 12a and the drain 12b is formed on the substrate 11. The gate 13 typically includes an oxidized layer 14, a poly silicon layer 15, and a metal layer 16. A probe biomolecule 17 is bonded to the metal layer 16 of the gate 13. When a predetermined target biomolecule is bonded to the probe biomolecule 17 by, for example, hydrogen bonding, the current changes. The change in the current is measured and the bonding of the probe biomolecule 17 and the predetermined target biomolecule can be identified.
The above-described conventional techniques, however, cannot retain reliable accuracy and be reliably reproduced when charged biomolecules are sensed in an electrolyte 10. In detail, the target biomolecule is bonded to the probe biomolecule 17 immobilized on the surface of the gate 13 in an electrolyte of a bioFET. At this time, when charged biomolecules are separated from the surface of the gate 13 by a debye length or farther, the charged biomolecules cannot affect an electric potential at the surface of the gate 13 due to ionic shielding of ions adjacent to biomolecules in the electrolyte 10, and it is difficult to accurately measure the electrical potential of the surface of the gate 13. Accordingly, the detection of immobilization of the probe biomolecule 17 to the surface of the gate 13 and hybridization of the probe biomolecule 17 with the target biomolecule has low reproducibility and accuracy.
In order to prevent ionic shielding, ionic concentration of the electrolyte can be decreased to increase the debye length. However, when the ionic concentration is decreased, for example, when the concentration of NaCl is 0.01 M or less, the detection efficiency decreases.
U.S. Pat. No. 5,466,348 discloses an apparatus for sensing biomolecules in a dry environment to prevent ion shielding. However, practical use of the apparatus is limited and a separate apparatus is required.
In U.S. Pat. No. 6,203,981, two transistor are used to decrease noise, and thus, increase the S/N ratio. However, desired effects of signal amplification cannot be obtained.
In U.S. Pat. No. 6,482,639 B2, charged biomolecules and uncharged biomoleclues are detected through a change in capacitance due to adsorption/bonding of biomolecules between a reference electrode and a gate surface. However, reproducibility and accuracy for sensing using a bioFET are not reliable.